GlaxoSmithKline has a new once-daily inhaled corticosteroid called fluticasone furoate; it has enhanced affinity for glucocorticoid receptors and a longer duration of action compared to the commonly-used fluticasone propionate, which must be taken twice daily to achieve a steady bioavailable concentration. In the January Thorax, William Busse et al report the findings of a Phase [… read more]
Allergic rhinitis is mostly just an annoyance for 400 million people worldwide, but the condition can predispose to frequent upper respiratory infections, and worsen asthma; Alexander Greiner et al tell you what you need to know in this review in Lancet. Incidence peaks in the teenage years. The nasal inflammation of allergic rhinitis synergizes with [… read more]
In July 2011, FDA approved indacaterol, Novartis’s new once-daily long-acting beta agonist, for the treatment of chronic obstructive pulmonary disease. In contrast to its European counterpart (EMA), which approved indacaterol there at doses up to 300 mcg, FDA only approved indacaterol in the 75 mcg daily dose. The FDA’s Badrul Chowdhury explains why in the [… read more]
Wechsler et al randomized and crossed-over 39 subjects with stable asthma to sequentially receive treatment with 1) albuterol; 2) fake albuterol; 3) fake acupuncture, or 4) nothing. Although albuterol improved stable asthmatic subjects’ FEV1 by 20%, they perceived equal improvement in subjective symptoms when given a sham inhaler or a sham acupuncture treatment. (These also [… read more]
Grainge et al collected bronchial biopsies from 48 allergic asthmatics, then randomly gave them either inhaled dust mite allergen; methacholine; saline (control); or albuterol followed by methacholine (control). Those inhaling allergen or methacholine had immediate bronchoconstriction, followed by an increase in bronchial wall thickness (on repeat bronchial biopsy 4 days later) compared to controls. Dogma [… read more]
Morales et al queried a database of 53,994 UK asthma patients, finding 1527 who were prescribed beta blockers, 441 with a brand-new prescription. The rate of oral steroid use in the 2 weeks prior to beta-blocker commencement was the same as in the 2 weeks after (0.9%). They did not examine exacerbation rates or steroid [… read more]
Even my neighbor’s cat knows that giving high-concentration oxygen to people with COPD and acute hypercapneic respiratory failure can cause them to hypoventilate further, causing life-threatening respiratory failure. (And he’s not even a very smart cat.) Perrin, Beasley et al asked, does a similar mechanism operate in severe asthma exacerbations? They randomized 106 patients presenting [… read more]
This is a great article by a leader in the field (William Busse), and it’s free — you should download it and save it. His theme is “Filling in the information gaps,” and there are a lot of them. Filling them in will take a lot of time, funding, and a bigger shovel than anyone’s got right now. A [… read more]
People with asthma have an impressive and frustrating variability in their response to treatment, with corticosteroids and other drugs. As many as 40% of people with asthma don’t respond to inhaled steroids. Asthma’s familial basis is well-known: 60% of the variability in the response to albuterol may be inherited, and more than 80% of the treatment response to [… read more]
Confirming my suspicions that when it comes to severe asthma, we are all mostly just faking it, this consensus guideline from the European U-BIOPRED public/private consortium points out how little we really know about this complex and variable illness. There are a couple of helpful tables and algorithms here to help you make sure you’ve [… read more]
Leukotrienes are important inflammatory mediators in both chronic asthma and acute exacerbations. Well-known for their benefits in the management of chronic asthma, leukotriene receptor antagonists haven’t been tested in acute asthma. Ramsay et al randomized 87 adults admitted to the hospital for asthma exacerbations to receive daily montelukast 10 mg or placebo for 4 weeks, [… read more]
Surprisingly little is really known about airway remodeling in asthma, including its clinical course, or how treatment may modify it. Two examples: rather than occurring as a late sequela of unchecked inflammation, numerous recent studies show remodeling can occur in tandem with inflammation starting in early childhood. A recent NEJM article generates the hypothesis that [… read more]
Asthma’s complex and protean inflammatory processes vary between individuals, some of whom have elevated levels of interleukin-13 despite maximal treatment with inhaled steroids. IL-13 prompts airway epithelial cells to secrete periostin, which acts on fibroblasts and may contribute to airway remodeling in asthma. Lebrikizumab is a monoclonal antibody inhibiting IL-13. Corren et al used a [… read more]
In a crossover design, Kerstjens et al randomized 100 patients with uncontrolled severe asthma (despite high dose inhaled corticosteroid and long-acting beta agonist) to also receive tiotropium 5 mcg, tiotropium 10 mcg, and placebo (in random order) for 8 weeks each. Tiotropium improved peak FEV1 at both doses (increase of 139-170 mL, the primary endpoint). [… read more]
An excellent free full text review by Paul O’Byrne. What’s new here: Did you know that formoterol is used as a first-line rescue inhaler, outside the U.S.? Formoterol has a steeper dose-response curve than salmeterol: repeated doses have an additive bronchodilator effect. The use of budesonide/formoterol as a combination maintenance AND rescue inhaler (added prn [… read more]
Under mandate by the FDA to answer lingering questions about long-acting beta agonists’ safety for treatment of asthma, four major pharma firms will launch five large randomized trials comparing inhaled corticosteroid / long-acting beta agonist combination products vs. ICS alone. The trials (4 in adults, 1 in kids) will enroll >50,000 people starting this year, [… read more]
Hashimoto et al randomized 95 adults taking chronic prednisone for severe asthma to usual care or home-tapering guided by spirometry, exhaled nitric oxide (from hand-held devices) and a symptom diary. The self-tapered group used significantly less prednisone without a worsening in symptoms (primary endpoint), hospitalizations or exacerbations (2′ endpoints). (n=95) Thorax 2011;66:514-520.
Yao et al report a meta-analysis of 8 studies (n=728) measured hydrogen peroxide in exhaled breath condensate in asthmatics. Overall, concentration of H2O2 did distinguish asthmatics from non-asthmatics, and H2O2 levels correlated with worsening asthma control and with declining FEV1. CHEST 2011;140:108-116.
Hargreave and Nair (PRO) argue the boutique technique is underrated and underused, citing trials showing improvement in severe asthma outcomes when sputum eosinophils are used to guide therapy (1, 2, and studies on IL-5 blockers). Peters (CON) questions the findings of those trials, doubts eosinophil count adds to clinical measures of asthma control, and compares [… read more]
Chinellato et al report that among 45 children with intermittent asthma, only 11% had “adequate” levels of 25-OH-vitamin D (30-40 ng/mL). Low vitamin D was associated with low FEV1, FVC, and exercise bronchospasm. Eur Resp J 2011;37:1366-1370.
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